envudeucitinib (ESK-001) / Alumis - LARVOL DELTA

An Investigational Study to Evaluate the Cardiac Safety Assessment (TQTc Study) of ESK-001 (clinicaltrials.gov) - P1 | N=52 | Completed | Sponsor: Alumis Inc

New P1 trial

Alumis Inc announced positive topline results from ONWARD1 and ONWARD2, 2 parallel, global, randomized, double-blind phase 3 trials designed to assess the efficacy and safety of envudeucitinib over 24 weeks. (DermatologyTimes) - "According to the topline results, envudeucitinib met all primary and secondary endpoints in both trials with high statistical significance compared with placebo (p < 0.0001)...Across ONWARD1 and ONWARD2, an average of 74% of patients treated with envudeucitinib achieved PASI 75 at week 16, and 59% achieved sPGA 0/1. The placebo-adjusted response rates for both co-primary endpoints were reported to be consistent between the 2 studies, supporting reproducibility of the findings...Based on the phase 3 results, Alumis plans to submit a New Drug Application to the US FDA in the second half of this year and to present more detailed trial data at an upcoming medical meeting."

FDA filing • P3 data: top line • Psoriasis

An Investigational Study of ESK-001 in Participants With Normal Renal Function and Participants With Mild, Moderate, and Severe Impaired Renal Function (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Alumis Inc | Recruiting ➔ Completed | N=48 ➔ 16 | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ Aug 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Renal Disease

Transcriptomic and Proteomic Modulation in Psoriatic Skin Following Envudeucitinib Treatment: Subgroup Analysis of a Phase 2 Randomized Trial (ISDS 2025) - P2 | "In moderate-to-severe psoriasis, envudeucitinib at 40mg QD and 40mg BID produced robust suppression of pathogenic Th1, Th17, and interferon-related pathways at transcriptomic and proteomic levels. These findings present further evidence of TYK2 inhibition as an effective treatment for moderate-to-severe plaque psoriasis."

Clinical • P2 data • Dermatology • Immune Modulation • Immunology • Pruritus • Psoriasis • AXL • CCL20 • CCL3 • CXCL11 • CXCL8 • CXCL9 • IFIT2 • IFNG • IL12B • IL17A • IL22 • IL6R • ITGB2 • MX1 • OASL • TNFRSF1A • TYK2 • XCL2

Anticipated Milestones (GlobeNewswire) - "Envu: topline data from ONWARD1 and ONWARD2 in moderate-to-severe plaque psoriasis are expected early in the first quarter of 2026; Envu: topline data from LUMUS in SLE are expected in the third quarter of 2026; Envu: Alumis expects to establish a once-daily formulation in 2025. A-005: initiation of a Phase 2 clinical trial in multiple sclerosis is anticipated in the first half of 2026; Lonigutamab: the lonigutamab development program continues to be evaluated; Third internally-developed program: Phase 1 clinical data is anticipated in the second half of 2026."

Clinical data • New P2 trial • Multiple Sclerosis • Psoriasis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Response to Papp et al., "Efficacy and safety of ESK-001, a highly selective, oral allosteric TYK2 inhibitor, in patients with moderate-to-severe plaque psoriasis: 52-week results from the long-term Phase 2 study in patients who participated in the Phase 2 STRIDE study". (PubMed, J Am Acad Dermatol) - No abstract available

Journal • P2 data • Dermatology • Immunology • Psoriasis • TYK2

Safety and Efficacy of envudeucitinib, a highly selective, oral allosteric TYK2 inhibitor, in patients with moderate-to-severe plaque psoriasis: Results from the 52-week open-label extension period of the Phase 2 STRIDE study. (PubMed, J Am Acad Dermatol) - P2 | "Envudeucitinib 40 mg BID in adults with moderate-to-severe plaque psoriasis demonstrated increasing and durable improvements in skin clearance and pruritus and was well-tolerated throughout 52 weeks of treatment."

Journal • P2 data • Dermatology • Immunology • Pruritus • Psoriasis • TYK2

Treat-to-Target Outcomes With ESK-001 in Moderate-to-Severe Plaque Psoriasis: Results From the Phase 2 STRIDE & Open-Label Extension Studies (ESDR 2025) - "Treatment with ESK-001 resulted in meaningful clinical improvements in patients with moderate-to-severe plaque psoriasis. Patients achieved stringent absolute thresholds in STRIDE, with continued PASI and BSA improvements and DLQI maintenance through 52 weeks of treatment in OLE."

Clinical • P2 data • Dermatology • Immunology • Psoriasis • TYK2

Envudeucitinib designated generic name for ESK-001 (GlobeNewswire)

Commercial • Immunology • Psoriasis • Systemic Lupus Erythematosus

Alumis Completes Patient Enrollment in the Global LUMUS Phase 2b Trial of ESK-001, a Next-Generation Oral TYK2 Inhibitor for the Treatment of Systemic Lupus Erythematosus (GlobeNewswire) - "Alumis...announced the completion of patient enrollment in its global LUMUS Phase 2b trial of ESK-001, a highly selective, next-generation oral tyrosine kinase 2 (TYK2) inhibitor, for the treatment of systemic lupus erythematosus (SLE), the most common form of lupus....The global LUMUS Phase 2b trial is a randomized, double-blind, placebo-controlled study evaluating multiple doses of ESK-001 in adults with moderately-to-severely active, autoantibody-positive SLE. The trial enrolled 408 patients who are receiving ESK-001 or placebo for 48 weeks....Topline readout expected in Q3 2026."

Enrollment closed • P2b data • Systemic Lupus Erythematosus

LUMUS: Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=408 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Highly selective, allosteric inhibition of TYK2 with oral ESK-001 in patients with moderate-to-severe plaque psoriasis: Results from STRIDE, a 12-week, randomized, double-blinded, placebo-controlled, dose-ranging Phase 2 study. (PubMed, J Am Acad Dermatol) - P2 | "ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose in patients with psoriasis and was well-tolerated."

Clinical • Journal • P2 data • Dermatology • Immunology • Psoriasis • TYK2

...Anticipated Milestones (GlobeNewswire) - "Topline data from ONWARD1 and ONWARD2 are expected early in the first quarter of 2026...A-005 is anticipated to enter a Phase 2 clinical trial in multiple sclerosis in the first half of 2026...Alumis anticipates Phase 1 clinical data from the next program in the second half of 2026."

Clinical data • New P2 trial • Multiple Sclerosis • Psoriasis

ONWARD2: A Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001 (clinicaltrials.gov) - P3 | N=840 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Dec 2025 | Trial primary completion date: May 2026 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Dermatology • Immunology • Psoriasis

ONWARD1: A Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P3 | N=840 | Active, not recruiting | Sponsor: Alumis Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Dec 2025 | Trial primary completion date: May 2026 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Dermatology • Immunology • Psoriasis

Alumis Completes Enrollment of Pivotal Phase 3 ONWARD Clinical Program of Lead Candidate ESK-001, a Highly Selective, Next-Generation Oral TYK2 Inhibitor for the Treatment of Moderate-to-Severe Plaque Psoriasis (GlobeNewswire) - "Alumis Inc...announced the completion of patient enrollment in its pivotal Phase 3 ONWARD clinical program of ESK-001 for the treatment of moderate-to-severe plaque psoriasis...'With over 1,700 patients enrolled across the two trials, this milestone reflects the dedication of our patients, investigators, and the Alumis team'....The Phase 3 ONWARD clinical program consists of two parallel global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis."

Enrollment closed • Psoriasis

Alumis Completes Enrollment of Pivotal Phase 3 ONWARD Clinical Program of Lead Candidate ESK-001, a Highly Selective, Next-Generation Oral TYK2 Inhibitor for the Treatment of Moderate-to-Severe Plaque Psoriasis (Firstwordpharma Press Release) - "Alumis Inc...announced the completion of patient enrollment in its pivotal Phase 3 ONWARD clinical program of ESK-001 for the treatment of moderate-to-severe plaque psoriasis...'With over 1,700 patients enrolled across the two trials, this milestone reflects the dedication of our patients, investigators, and the Alumis team, whose efforts have made it possible. We remain on track to report topline results in early Q1 2026, bringing us closer to delivering transformative treatment solutions for patients in need.'....The Phase 3 ONWARD clinical program consists of two parallel global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis."

Enrollment closed • P3 data: top line • Psoriasis

Maximal and sustained TYK2 inhibition: The key to higher efficacy with oral allosteric inhibitors (SID 2025) - "The 40 mg BID dose of ESK-001 achieved >24-hour IC90 coverage and complete SIGLEC1 suppression in patients, suggesting that maximal inhibition results in higher efficacy. These findings support 40 mg BID as the optimal regimen for treating psoriasis."

Clinical • Dermatology • Immunology • Psoriasis • IFNA1 • IL12A • IL23A • SIGLEC1 • TYK2

ESK-001, an allosteric TYK2 inhibitor, inhibits TYK2-and psoriasis-relevant biomarkers in skin using spatial transcriptomics (SID 2025) - "Disease-relevant bulk and spatial transcriptomic analysis in skin tissue shows decreased expression of key psoriasis biomarkers in non-lesional skin compared to lesional. Analysis after ESK-001 administration further indicates a return of key psoriasis biomarkers to nonlesional baseline levels."

Biomarker • Dermatology • Immunology • Psoriasis • IL17A • KRT16 • TYK2

Anticipated Milestones (GlobeNewswire) - "2025: Planned merger with ACELYRIN: Closing of merger with ACELYRIN (2Q 2025); A-005: Initiation of Phase 2 clinical trial in multiple sclerosis (MS); Lonigutamab: Finalize clinical development plan following the closing of the merger with ACELYRIN (mid-2025); Third pipeline program: Investigational New Drug Application filing for third clinical candidate...2026: ESK-001: Psoriasis Phase 3 topline data (1Q 2026); ESK-001: SLE Phase 2b topline data; A-005: MS Phase 2 topline data."

Clinical data • M&A • New P2 trial • Pipeline update • Multiple Sclerosis • Systemic Lupus Erythematosus • Thyroid Eye Disease

An Investigational Study of ESK-001 in Participants With Normal Renal Function and Participants With Mild, Moderate, and Severe Impaired Renal Function (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Alumis Inc

New P1 trial • Renal Disease

An Investigational Study of ESK-001 in Participants With Normal Liver Function and Participants With Mild, Moderate, and Severe Liver Damage (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Alumis Inc

New P1 trial • Hepatology

Alumis and ACELYRIN Announce Amended Merger Agreement (GlobeNewswire) - "Merger maximizes the potential value for ACELYRIN stockholders and creates a stronger combined company, best-positioned to realize long-term value of multiple late-stage assets...Alumis Inc...and ACELYRIN, INC...announced an amendment to the existing terms of their previously announced merger agreement...Under the terms of the amended agreement, ACELYRIN stockholders will now receive 0.4814 shares of Alumis common stock for each share of ACELYRIN common stock owned, representing a meaningful increase in the ownership percentage of the combined company over the original definitive merger agreement....'We continue to believe that this combination is the most value-maximizing path forward for ACELYRIN stockholders and that Alumis is the right partner to optimize development of lonigutamab.'"

M&A • Immunology • Multiple Sclerosis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Alumis and ACELYRIN File Joint Definitive Proxy Statement for Proposed Merger (GlobeNewswire) - "Alumis Inc...and ACELYRIN, INC...have jointly filed a definitive proxy statement/prospectus with the U.S. Securities and Exchange Commission in connection with the proposed merger of the two companies. The joint proxy statement/prospectus are being mailed to all Alumis and ACELYRIN stockholders entitled to vote...Topline data from Phase 2b LUMUS trial in systemic lupus erythematosus on track for readout in 2026; Phase 2 clinical trial initiation for Alumis’ A-005 in MS...Pro forma cash of approximately $737 million as of December 31, 2024, provides runway into 2027, beyond multiple expected clinical readouts....By combining assets, resources and talent, including members of ACELYRIN’s lonigutamab program, the combined company will be well positioned to maximize the value of its pipeline."

M&A • New P2 trial • P2b data • Multiple Sclerosis • Systemic Lupus Erythematosus • Thyroid Eye Disease

Alumis and Kaken Pharmaceutical Announce Collaboration and Licensing Agreement for ESK-001 in Dermatology in Japan (GlobeNewswire) - "Alumis Inc...and Kaken Pharmaceutical Co., Ltd...announced that the companies have entered into a collaboration and licensing agreement to develop, manufacture and commercialize ESK-001, a highly selective, next-generation oral tyrosine kinase 2 (TYK2) inhibitor, for dermatology indications in Japan, with the option to expand the license to include rheumatological and gastrointestinal diseases...Under the terms of the agreement, Alumis will receive $40 million in upfront and near-term co-development payments in 2025 to 2026, with the potential to earn up to approximately $140 million in additional payments based on the achievement of milestones, and field option payments. Alumis is also eligible to receive tiered royalties ranging from the low double-digits into the twenties on aggregate net sales of ESK-001 in Japan. Kaken will be responsible for the clinical development, regulatory approvals and commercialization of ESK-001 in Japan, and Alumis will retain rights to..."

Licensing / partnership • Psoriasis • Systemic Lupus Erythematosus